Arginase 1 Deficiency
Conditions
Brief summary
This is an open-label, multicentre study to evaluate the safety, PK, and activity (PD) of weekly subcutaneous (SC) administration of pegzilarginase in subjects with ARG1-D who are \< 24 months of age. The study consists of a screening period of up to 4 weeks, a subsequent 12-week treatment period, and a safety follow-up period of 8 weeks.
Detailed description
CAEB1102-301A is an open-label, single-arm, non-controlled, repeat dosing, multicentre study to evaluate the safety, PK, and activity (PD) of weekly SC administration of pegzilarginase over 12 weeks in subjects with ARG1-D who are \< 24 months of age. This study will consist of: * A screening period of up to 4 weeks to ensure the subjects meet the study eligibility criteria and establish baseline plasma arginine * A treatment period of 12 weeks * A safety follow-up period of 8 weeks with visits 1 week and 8 weeks after the last dose.
Interventions
DRUGPegzilarginase
SC administration of pegzilarginase over 12 weeks in subjects with ARG1-D who are \< 24 months of age
Sponsors
Immedica Pharma AB
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Days to 24 Months
Healthy volunteers
No
Inclusion criteria
1. Subjects must be \< 24 months of age on the date of informed consent 2. Confirmed diagnosis of ARG1-D documented in medical records by at least 1 of the following methods: 1. elevated plasma arginine levels 2. a mutation analysis revealing a pathogenic variant 3. red blood cell (RBC) arginase activity 3. Subjects must weigh \> 8 kg due to clinical trial related blood collection volumes required 4. Written informed consent by parent/legal guardian, in accordance with national stipulations, which includes compliance with the requirements and restrictions listed in the informed consent form and in this protocol 5. At least one value of plasma arginine ≥ 180 μM during screening 6. Documented confirmation from the Investigator and/or dietitian that the subject can: 1. attempt to maintain a stable, age-appropriate level of protein consumption, including natural protein, and EAA supplementation within approximately ± 15% of dietitian recommended diet 2. attempt to maintain current use of ammonia scavengers, if prescribed
Exclusion criteria
1. Other medical condition(s) or comorbidity(ies) that, in the opinion of the Investigator, would interfere with study compliance or data interpretation 2. Hyperammonaemic episode (plasma ammonia levels \> 100 μM) with ≥ 1 symptom related to hyperammonaemia requiring hospitalisation or emergency room management within the 4 weeks before the first dose of study drug 3. Active infection requiring anti-infective therapy within \< 2 weeks before first dose of study drug 4. Known active infection with human immunodeficiency virus, hepatitis B, or hepatitis C 5. History of hypersensitivity to polyethylene glycol (PEG) or any of the excipients included in the study drug that, in the judgment of the Investigator, puts the subject at unacceptable risk for AEs 6. Currently participating in another therapeutic clinical study or has received any investigational agent within 30 days (or 5 half-lives, whichever is longer) prior to first dose of study drug 7. Previous liver or haematopoietic stem cell transplant 8. Use of botulinum toxin within 16 weeks prior to first dose
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Plasma Arginine Concentrations in Subjects <24 Months of Age With Arginase 1 Deficiency (ARG1-D). | From baseline up to 12 weeks. | To evaluate the effect of pegzilarginase on plasma arginine concentrations in subjects \<24 months of age with arginase 1 deficiency (ARG1-D). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic (PK) Profile of Pegzilarginase: Half-life (T½). | From baseline up to 12 weeks. Within 1 hour pre-dose a sample was taken on visits 1, 2, 4, 6, 8, 10, and 13. A post-dose sample was taken 12 - 48 hours after dosing on visits 2, 4, and 10. | PK parameters with evaluation of half-life (T½). |
| Pharmacokinetic (PK) Profile of Pegzilarginase: Maximum Observed Concentration (Tmax). | From baseline up to 12 weeks. Within 1 hour pre-dose a sample was taken on visits 1, 2, 4, 6, 8, 10, and 13. A post-dose sample was taken 12 - 48 hours after dosing on visits 2, 4, and 10. | PK parameters with evaluation on time to maximum observed concentration (Tmax). |
| Pharmacokinetic (PK) Profile of Pegzilarginase: Maximum Observed Concentration (Cmax). | From baseline up to 12 weeks. Within 1 hour pre-dose a sample was taken on visits 1, 2, 4, 6, 8, 10, and 13. A post-dose sample was taken 12 - 48 hours after dosing on visits 2, 4, and 10. | PK parameters with evaluation of maximum observed concentration (Cmax). |
| Pharmacokinetic (PK) Profile of Pegzilarginase: Area Under the Plasma Drug Concentration-time Curve. | From baseline up to 12 weeks. Within 1 hour pre-dose a sample was taken on visits 1, 2, 4, 6, 8, 10, and 13. A post-dose sample was taken 12 - 48 hours after dosing on visits 2, 4, and 10. | PK parameters with evaluation on area under the plasma drug concentration-time curve. |
| Pharmacodynamic (PD) Response of Pegzilarginase: Anti-drug Antibodies (ADAs). | From baseline up to 12 weeks. Samples taken on visit 1, 2, 4, 8 and 13 (pre-dose if on a dosing day). | PD response evaluation, anti-drug antibodies (ADAs). |
| Pharmacodynamic (PD) Response of Pegzilarginase: Levels of Plasma Arginine. | From baseline up to 12 weeks. Samples taken on visit 1, 2, 4, 8 and 13 (pre-dose if on a dosing day). | PD response evaluation, levels of plasma arginine. Arginine within guidance level. |
| Changes From Baseline in Physical Function: GMFM-66. | From baseline up to 12 weeks. | Changes in physical function after 12 weeks of pegzilarginase treatment as measured by Gross Motor Function Measure (GMFM)-66 Parts A through E (total score). The Gross Motor Function Measure (GMFM) utilize a 4-point scoring system for each item across dimensions A-E. The minimum score is 0; the maximum score is 198, with a higher score representing better gross motor function. |
Countries
Austria, Portugal, United Kingdom
Contacts
STUDY_DIRECTORMattias Rudebeck, PhD MSc BMedSc
Immedica Pharma AB
Participant flow
Recruitment details
Participants were enrolled at 3 different study sites between 30 August 2024 and 17 June 2025.
Pre-assignment details
All 3 participants were included in the study.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 20.3 Months STANDARD_DEVIATION 4.6 |
| Baseline plasma arginine levels | 228.67 μM STANDARD_DEVIATION 133.67 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 2 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 3 |
| other Total, other adverse events | 3 / 3 |
| serious Total, serious adverse events | 0 / 3 |
Outcome results
None listed